Project Summary There is keen interest in identifying the biochemical pathways that promote tumor intracerebral infiltration since members of these pathways serve as potential therapeutic targets. Unfortunately, the spatiotemporal nature of these pathways renders the application of conventional tools (over/under-expression of the proteins of interest, inhibitory compounds, etc.) inadequate for studying dynamic cell behavior. We seek to engineer and evaluate optogenetic analogs of cofilin, cofilin?s upstream activators (slingshot and chronophin), and cofilin?s upstream negative regulators (LIM protein kinase, the cAMP-dependent protein kinase, the p21 activated protein kinase, and rho-associated protein kinase). These species offer a means to correlate spatially-focused biochemical activity with dynamic cellular behavior including F-actin remodeling activity as well as migratory and invasive aptitudes.